Interpretive Handbook

Test
60720 :
Lysozyme (LYZ) Gene, Known Mutation

The systemic amyloidoses are a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis.

The hereditary amyloidoses comprise a group of autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been associated with hereditary forms of amyloidosis including those that encode transthyretin, apolipoprotein AI, apolipoprotein AII, fibrinogen alpha chain, gelsolin, cystatin C and lysozyme. Apolipoprotein AI, apolipoprotein AII, lysozyme, and fibrinogen amyloidosis present as non-neuropathic systemic amyloidosis, with renal dysfunction being the most prevalent manifestation.

LYZ-related familial visceral amyloidosis presents clinically with significant renal impairment. The renal dysfunction occurs at an early age and, in the absence of treatment, results in renal failure. Other manifestations of LYZ-related familial visceral amyloidosis include gastrointestinal involvement, cardiac disease, Sicca syndrome, and propensity towards petechiae, hemorrhage and hematoma, including hepatic hemorrhage. The bleeding tendency associated with LYZ-related familial visceral amyloidosis has included rupture of abdominal lymph nodes. Neuropathy is not a feature of LYZ-related familial visceral amyloidosis.

Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry might serve as a useful test preceding gene sequencing to better characterize the etiology of the amyloidosis, particularly in cases that are not clear clinically.

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order LYZMS / Lysozyme (LYZ) Gene, Full Gene Analysis.

Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with lysozyme (LYZ) gene-related familial visceral amyloidosis.

We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.

Predictive testing of an asymptomatic child is not recommended.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.